tbuckley/cabot-search huggingface dataset:
PB1875: NON-HEMATOPOIETIC CELL TRANSPLANT-RELATED VENO-OCCLUSIVE DISEASE/SINUSOIDAL OBSTRUCTION SYNDROME (VOD/SOS) IN SOLID TUMOR AND HEMATOLOGIC MALIGNANCIES: A SYSTEMATIC REVIEW
Authors: Fiona Stewart, Kimberly Ruiz, Malia Gill, Darsh Devani, Nicole Fusco, Lin Fan, Vian Amber, Raj Hanvesakul, Alexandra Gangi
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: VOD/SOS is a serious liver injury caused by toxic damage to sinusoidal endothelial cells. It has historically been associated with conditioning regimens preceding hematopoietic cell transplant (HCT), but little is known about its epidemiology and characteristics outside the HCT setting. Aims: We conducted a systematic review to examine the incidence, burden of illness, and management of non-HCT VOD/SOS. Methods: We searched MEDLINE, Embase (2002–2022), and relevant congress proceedings (2019–2022) for studies reporting incidence, diagnosis, clinical and patient characteristics, humanistic and economic burden, and treatments in non-HCT VOD/SOS. All study designs were eligible except case series of <5 patients. Pyrrolizidine alkaloid-induced VOD/SOS was excluded. Two authors independently screened titles/abstracts and full-text articles and assessed the methodological quality of studies. Data for predefined outcomes were extracted by one author and validated by a second author. Results: We identified 3544 records and included 80 studies; 58% were retrospective cohort studies. Sample sizes ranged from 5 to 12,941; 38% of the studies included >100 patients. The highest incidences of non-HCT VOD/SOS were in patients with colorectal liver metastases (CLM) treated with oxaliplatin-based chemotherapy (median 41%) and in patients treated with vincristine plus actinomycin D for Wilms tumor (median 14%). Non-HCT VOD/SOS cases were also identified in hematologic malignancies, including acute lymphoblastic leukemia (ALL) and acute myeloid lymphoma (AML) (Table 1). The proportion of cases described as moderate or severe ranged from 50%–100%. Diagnostic criteria were heterogenous. Rubbia-Brandt histological criteria were used in CLM. In other disease settings, including ALL and AML, diagnosis varied and was based on clinical criteria (eg, McDonald, Seattle, or Baltimore). Management of VOD/SOS included defibrotide, supportive therapy (eg, fluid restriction, blood products), and switching/pausing chemotherapy. No usable data were found on humanistic/economic burden. Summary/Conclusion: Non-HCT VOD/SOS occurs in diverse disease areas, including hematologic and solid tumor cancers. Lack of consensus regarding diagnosis of non-HCT VOD/SOS may indicate underdiagnosis. Given the seriousness of VOD/SOS, clinicians should be vigilant for VOD/SOS even in patients who have not undergone HCT. Defibrotide is approved for post-HCT VOD/SOS but there is no approved therapy for non-HCT VOD/SOS; future trials should focus on diagnosis and treatment outside the HCT setting, which represents a significant unmet need. A limitation of the current work is the suboptimal reporting and low methodological quality in some primary studies.Keywords: Veno-occlusive disease, Chemotherapy
PB2624: CLINICAL WHOLE EXOM SEQUENCING FOR CONGENITAL PLATELET DISORDERS: ONE SINGLE CENTER EXPERIENCE
Authors: Victor Portela Piñeiro, Adrian Mosquera-Orgueira, Eugenia Fernandez Mellid, Jose Angel Diaz Arias, Miguel Cid Lopez, Rocio Serrano Martin, Juan Carlos Vallejo Llamas
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Thrombocytopathies has been traditionally entities with few characterization laboratory tests and even fewer etiological diagnosis tools. New gene sequencing techniques may constitute a promising resource to identify some of the affected molecular pathways and consequently to establish a prognosis. One of them, clinical exome sequencing (Sophia Genetics), was used to sequence 4,728 genes associated with rare diseases and hereditary predisposition syndromes. Briefly, DNA was extracted and libraries were prepared using a capture-based assay. Aims: Evaluate the usefulness of clinical exome sequencing (CES) within the diagnostic algorithm of the congenital platelets disorders (CPD). Methods: After clinical, ISTH Bleeding Assessment Tool included, and either basic or specific laboratory evaluation, patients highly suspicious of thrombocytopathies in our Center were considered for clinical exome sequencing. Informed consent was given. Sequencing was performed in a NextSeq550 analyzer. The SOPHIA DDM platform was used for bioinformatics analysis. Pathogenic and likely pathogenic variants were called using Sophia’s filters and the ACMC classification. Manual curation and literature review was performed by an expert hematologist. Results: Between January 2020 and February 2023, there were performed CES in 26 patients, with an average age of 53 years, 73% of whom were women, and an average follow-up period of 8 years. We found 9 mutations described as pathogenic and concordant with the patient’s symptoms, some of them not previously described. Neither ISTH-BAT nor an inherited pattern were predictors of CES findings related with platelet disorders. Prolonged follow-up in consultations due to persistence of the symptomatology does seem to be relevant for the cost-effectiveness of the technique. Table 1: Characteristics of the patient with trhrombocytopathies who underwent CES in our center. (VWF: Von-Willebrand Factor, VF: Variant Frecuency, B-CCL: B-Chronic Lymphocytic Leukemia, MPN; Myeloproliferative Neoplasms, T-NHL: T- non-Hodgkin’s lymphoma, ITP: Immune Thrombocytopenia) Summary/Conclusion: CES is useful for typing congenital thrombocytopathies but a good clinical and temporal evaluation of the persistence of symptoms seems important for greater diagnostic yield. In our series, the possible hereditary pattern does not guarantee positive results in the study, the possible reasons being both bleeding diathesis not linked to platelets and functional thrombocytopathies not mediated by a single target in the platelet. Keywords: Inherited platelet disorders, Bernard-Soulier syndrome
Advanced Heart Failure Therapies for Hypertrophic Cardiomyopathy
Authors: Lusha W. Liang, Heidi S. Lumish, Lorenzo R. Sewanan, Yuichi J. Shimada, Mathew S. Maurer, Shepard D. Weiner, Gabriel Sayer, Nir Uriel, Kevin J. Clerkin
Journal: JACC Heart Failure (2023)
Quantitative Late Gadolinium Enhancement Cardiac Magnetic Resonance and Sudden Death in Hypertrophic Cardiomyopathy
Authors: Apostolos Kiaos, Georgios N. Daskalopoulos, Vasileios Kamperidis, Antonios Ziakas, Georgios Efthimiadis, Theodoros D. Karamitsos
Journal: JACC. Cardiovascular imaging (2023)
PB2678: THE PROGNOSTIC SIGNIFICANCE OF CONTROLLING NUTRITIONAL STATUS AND SARCOPENIA IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Se‑il Go, Sungwoo Park, Eun-Jeong Jeong, Gyeong-Won Lee
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: The Controlling Nutritional Status (CONUT) score has been shown to be a valuable prognostic index for diffuse large B-cell lymphoma (DLBCL) patients. However, it is unclear whether its prognostic role is affected by the presence of sarcopenia. Aims: This retrospective study aimed to investigate the validity of the CONUT score as a prognostic indicator for DLBCL patients with or without sarcopenia. Methods: We reviewed the medical records of 305 DLBCL patients who received R-CHOP immunochemotherapy. Sarcopenia was determined using the third lumbar skeletal muscle index from CT imaging. The CONUT score was calculated based on the patients’ baseline serum albumin, total cholesterol, and absolute lymphocyte counts. Patients were classified into normal/mild (n=219) and moderate/severe (n=86) CONUT groups based on the original criteria. Results: The complete response rate decreased progressively as the severity of the CONUT score increased (normal: 87.5%, mild: 77.0%, moderate: 60.3%, severe: 50.0%). The moderate/severe CONUT group had a higher incidence of ≥grade 3 thrombocytopenia (45.4% vs. 24.2%), febrile neutropenia (44.2% vs. 23.7%), ≥grade 3 non-hematologic toxicity (41.9% vs. 29.2%), and early treatment discontinuation (30.2% vs. 13.2%) than the normal/mild CONUT group. Median progression-free survival (13 vs. 163 months) and overall survival (18 vs. 163 months) were significantly shorter in the moderate/severe CONUT group compared to the normal/mild CONUT group. Regardless of sarcopenia status, the moderate/severe CONUT group had a worse prognosis. Multivariable analysis, which adjusted for several variables, including the NCCN-International Prognostic Index, showed that both moderate/severe CONUT score and sarcopenia were independent poor prognostic factors. In patients with moderate/severe CONUT score and sarcopenia, the median overall survival was only 7.3 months. Summary/Conclusion: The study found that the moderate/severe CONUT group had worse clinical outcomes and shorter survival compared to the normal/mild CONUT group. The CONUT score was a valuable prognostic indicator regardless of the presence of sarcopenia.Keywords: Diffuse large B cell lymphoma
PB2704: PREDICTING HEMATOLOGICAL MALIGNANCIES USING COMPLETE BLOOD CELL COUNTS FROM PRIMARY CARE
Authors: Mathilde Christensen, Michael Charles Sachs, Gustav Jonzon, Erin Gabriel, Volkert Siersma, Margit Kriegbaum, Lene Sofie Granfeldt Østgård, Kirsten Grønbæk, Christen Lykkegaard Andersen
Journal: HemaSphere (2023)

Topic: 36. Ethics and health economics Background: Hematological malignancies are rare and primary care physicians often only encounter a few cases throughout their career. As optimal referral to secondary care often relies on a combination of pattern recognition and fulfilling referral criteria, it may be challenging for non-hematologists to stay updated and able to recognize hematological cancers in early stages. Aims: To create an algorithm capable of screening complete blood cell counts for impending hematological malignancy using machine learning. Methods: We included adult patients with no history of hematological malignancy, and at least one complete blood cell count (CBC) in the Copenhagen Primary Care Laboratory (CopLab) Database encompassing all laboratory results from the primary care sector of the greater Copenhagen area (20 % of the Danish population) from 2000-2016. Hematological malignancies were identified through the Danish Cancer Register. The CBC furthest from but within 6, 12 and 24 months of a cancer event were included and matched to up to 5 non-cancer events (death, emigration or nothing), for a person with the same sex and within 4 years of age of the cancer patient. Up to 5 years of CBC history was included. The data was split 60:40 into training and validation sets based on a unique personal identifier (CPR-number). The model was trained using SuperLearner; fitting and pre-validating a library of 4 methods, with or without the 5-year CBC history. The optimal ensemble was then estimated using LASSO. Receiver Operating Characteristic (ROC) curves were estimated to assess the algorithms’ discriminatory value. Decision curves were then estimated to assess the net benefit (true positive fraction – false positive fraction x (p/(1-p)) as a function of the threshold probability p. Results: 663,184 patients were included. Areas under the ROC curves (AUC) for malignancy within 6, 12 and 24 months were 0.84, 0.81 and 0.74, respectively. If the 5-year CBC history was included, the AUCs increased to 0.85 (6 mo.), 0.81 (12 mo.) and 0.75 (24 mo.), respectively. The decision curve analysis indicated a positive net benefit of the algorithm over a wide range of threshold probabilities, and clearly indicates superiority to the WHO criteria for referral. Summary/Conclusion: Risk prediction of any hematologic malignancy within 6 months can be done with high accuracy based on current CBC with no marked benefits of including a 5-year CBC history. Accuracy declines slightly when looking at 1 year and 3 years. Risk prediction models are well-calibrated in this selected subsample, appearing to out-perform the current WHO referral criteria in this setting. Keywords: Prediction, Machine learning
Noninvasive Imaging Methods for Quantification of Pulmonary Edema and Congestion
Authors: Thomas Lindow, Scott Quadrelli, Martin Ugander
Journal: JACC. Cardiovascular imaging (2023)

Quantification of pulmonary edema and congestion is important to guide diagnosis and risk stratification, and to objectively evaluate new therapies in heart failure. Herein, we review the validation, diagnostic performance, and clinical utility of noninvasive imaging modalities in this setting, including chest x-ray, lung ultrasound (LUS), computed tomography (CT), nuclear medicine imaging methods (positron emission tomography [PET], single photon emission CT), and magnetic resonance imaging (MRI). LUS is a clinically useful bedside modality, and fully quantitative methods (CT, MRI, PET) are likely to be important contributors to a more accurate and precise evaluation of new heart failure therapies and for clinical use in conjunction with cardiac imaging. There are only a limited number of studies evaluating pulmonary congestion during stress. Taken together, noninvasive imaging of pulmonary congestion provides utility for both clinical and research assessment, and continued refinement of methodologic accuracy, validation, and workflow has the potential to increase broader clinical adoption.
PB2257: OUTCOME AND PROGNOSTIC FACTORS OF PEDIATRIC PATIENTS WITH HODGKIN LYMPHOMA: A SINGLE-CENTER EXPERIENCE
Authors: Nesreen Ali, Mohamed Mansour, Ehab Khalil, Emad Ebeid
Journal: HemaSphere (2023)

Topic: 17. Hodgkin lymphoma - Clinical Background: Hodgkin’s lymphoma (HL) is a highly curable malignant tumor. Risk-adapted treatment for children with HL aims to maximize survival while minimizing toxicity. Aims: The purpose of this study was to evaluate the outcome and prognostic characteristics of Egyptian pediatric patients with classic HL who were treated at the National Cancer Institute (NCI), Cairo University. Methods: All newly diagnosed cases of classic HL treated between January 2016 and December 2018 were included in this study. Results: The median age at initial presentation was eight years for 69 eligible individuals, with a male-to-female ratio of 4.7:1. 18% of patients had an elevated ESR (> 50), 42% had more than three lymph node group involvements, 18.8% had bulky disease, 52.2% were at an advanced stage, and 34% had B-symptoms. >15 years of age, B-symptoms, >3 LN groups involved, extra-nodal involvement, and advanced stages all significantly affected the survival rate (p-values = 0.03, 0.033, 0.008, 0.017, and 0.032). There was no statistically significant difference between patients who got combined modality therapy (CMT) and those who received chemotherapy alone (3-year OS and EFS were 95.5% and 87.6% vs. 89.9% and 83.3%: p-values of 0.70 and 0.90). Rapid early response (RER) is one of the most important prognostic factors (3-year OS and EFS in patients with interim negative positron emission tomography–computed tomography (PET-CT): 94.7% and 84.8% vs. 74.1% and 74.1% in patients with interim positive PET-CT: p values of 0.06 and 0.35). There was no statistically significant survival difference between patients with a negative interim PET who got CMT and those who had chemotherapy alone (3-year OS and EFS: 100% and 88.2% vs. 95% and 90%; P-values: 0.35 and 0.70, respectively). There was no significant difference between those who received 15 Gy and those who received a dose of 20 Gy or higher. The 3-year OS was (93.3% & 100%) and EFS (was 74.3% and 100%) with P-value. (P=0.495 & 0.196%). At the end of the study, the OS and EFS at three years for the whole group were 91.9% and 83.6%, respectively. Summary/Conclusion: Treatment with risk and response adaptive treatment should be the standard of care for treating pediatric patients with HL. The omission of radiotherapy in those with RER can be safely done without compromising treatment results. Keywords: Children, Hodgkin’s lymphoma, Outcome
Identifying molecular phenotypes in sepsis: an analysis of two prospective observational cohorts and secondary analysis of two randomised controlled trials
Authors: Pratik Sinha, V Eric Kerchberger, Andrew Willmore, Julia Chambers, Hanjing Zhuo, Jason Abbott, Chayse Jones, Nancy Wickersham, Nelson Wu, Lucile Neyton, Charles R Langelier, Eran Mick, June He, Alejandra Jauregui, Matthew M Churpek, Antonio D Gomez, Carolyn M Hendrickson, Kirsten N Kangelaris, Aartik Sarma, Aleksandra Leligdowicz, Kevin L Delucchi, Kathleen D Liu, James A Russell, Michael A Matthay, Keith R Walley, Lorraine B Ware, Carolyn S Calfee
Journal: The Lancet Respiratory Medicine (2023)
The Diagnosis and Non-pharmacological Management of Acute Kidney Injury in Patients with Cirrhosis
Authors: Nikhilesh R. Mazumder, Shilpa Junna, Pratima Sharma
Journal: Clinical Gastroenterology and Hepatology (2023)

Acute kidney injury in patients with cirrhosis is quite common, and is seen in up to 50% of patients hospitalized for decompensated cirrhosis. Causes of acute kidney injury include prerenal, renal, or postrenal etiologies. The diagnosis and early institution of nonpharmacologic and pharmacologic management are key to the recovery of renal function. The objective of this review is to provide a practical approach to the use of diagnostic biomarkers and highlight the nonpharmacologic management and prevention of acute kidney injury.
FDA-cleared artificial intelligence and machine learning-based medical devices and their 510(k) predicate networks
Authors: Urs J Muehlematter, Christian Bluethgen, Kerstin N Vokinger
Journal: The Lancet Digital Health (2023)

The US Food and Drug Administration is clearing an increasing number of artificial intelligence and machine learning (AI/ML)-based medical devices through the 510(k) pathway. This pathway allows clearance if the device is substantially equivalent to a former cleared device (ie, predicate). We analysed the predicate networks of cleared AI/ML-based medical devices (cleared between 2019 and 2021), their underlying tasks, and recalls. More than a third of cleared AI/ML-based medical devices originated from non-AI/ML-based medical devices in the first generation. Devices with the longest time since the last predicate device with an AI/ML component were haematology (2001), radiology (2001), and cardiovascular devices (2008). Especially for devices in radiology, the AI/ML tasks changed frequently along the device's predicate network, raising safety concerns. To date, only a few recalls might have affected the AI/ML components. To improve patient care, a stronger focus should be placed on the distinctive characteristics of AI/ML when defining substantial equivalence between a new AI/ML-based medical device and predicate devices.
Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study
Authors: Ruijie Tang, Hengrui Liang, Yuchen Guo, Zhigang Li, Zhichao Liu, Xu Lin, Zeping Yan, Jun Liu, Xin Xu, Wenlong Shao, Shuben Li, Wenhua Liang, Wei Wang, Fei Cui, Huanghe He, Chao Yang, Long Jiang, Haixuan Wang, Huai Chen, Chenguang Guo, Haipeng Zhang, Zebin Gao, Yuwei He, Xiangru Chen, Lei Zhao, Hong Yu, Jian Hu, Jiangang Zhao, Bin Li, Ci Yin, Wenjie Mao, Wanli Lin, Yujie Xie, Jixian Liu, Xiaoqiang Li, Dingwang Wu, Qinghua Hou, Yongbing Chen, Donglai Chen, Yuhang Xue, Yi Liang, Wenfang Tang, Qi Wang, Encheng Li, Hongxu Liu, Guan Wang, Pingwen Yu, Chun Chen, Bin Zheng, Hao Chen, Zhe Zhang, Lunqing Wang, Ailin Wang, Zongqi Li, Junke Fu, Guangjian Zhang, Jia Zhang, Bohao Liu, Jian Zhao, Boyun Deng, Yongtao Han, Xuefeng Leng, Zhiyu Li, Man Zhang, Changling Liu, Tianhu Wang, Zhilin Luo, Chenglin Yang, Xiaotong Guo, Kai Ma, Lixu Wang, Wenjun Jiang, Xu Han, Qing Wang, Kun Qiao, Zhaohua Xia, Shuo Zheng, Chenyang Xu, Jidong Peng, Shilong Wu, Zhifeng Zhang, Haoda Huang, Dazhi Pang, Qiao Liu, Jinglong Li, Xueru Ding, Xiang Liu, Liucheng Zhong, Yutong Lu, Feng Xu, Qionghai Dai, Jianxing He
Journal: The Lancet Digital Health (2023)
Digital health funding for COVID-19 vaccine deployment across four major donor agencies
Authors: Daniel Helldén, Sophia Tesfaye, Carine Gachen, Ann Lindstrand, Karin Källander
Journal: The Lancet Digital Health (2023)

The international response to the COVID-19 pandemic provided opportunities for countries to use digital technologies for vaccine deployment and associated activities, but misaligned digital investments could weaken or fragment national systems. In this review of 311 funding applications from 120 country governments to four donor agencies (UNICEF; Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and the World Bank) up to May 1, 2022, we found that 272 (87%) of the applications included at least one digital aspect and that substantial funding has been dedicated towards digital aspects from donors. The majority of digital aspects concerned immunisation information systems, vaccine acceptance and uptake, and COVID-19 surveillance. As the global community sets its sights on a COVID-19-free world, continued coordinated investments in digital health and health information systems for pandemic preparedness and response will be key to strengthening the resilience of health systems.
Predicting 10-year breast cancer mortality risk in the general female population in England: a model development and validation study
Authors: Ash Kieran Clift, Gary S Collins, Simon Lord, Stavros Petrou, David Dodwell, Michael Brady, Julia Hippisley-Cox
Journal: The Lancet Digital Health (2023)

BackgroundIdentifying female individuals at highest risk of developing life-threatening breast cancers could inform novel stratified early detection and prevention strategies to reduce breast cancer mortality, rather than only considering cancer incidence. We aimed to develop a prognostic model that accurately predicts the 10-year risk of breast cancer mortality in female individuals without breast cancer at baseline.MethodsIn this model development and validation study, we used an open cohort study from the QResearch primary care database, which was linked to secondary care and national cancer and mortality registers in England, UK. The data extracted were from female individuals aged 20–90 years without previous breast cancer or ductal carcinoma in situ who entered the cohort between Jan 1, 2000, and Dec 31, 2020. The primary outcome was breast cancer-related death, which was assessed in the full dataset. Cox proportional hazards, competing risks regression, XGBoost, and neural network modelling approaches were used to predict the risk of breast cancer death within 10 years using routinely collected health-care data. Death due to causes other than breast cancer was the competing risk. Internal–external validation was used to evaluate prognostic model performance (using Harrell's C, calibration slope, and calibration in the large), performance heterogeneity, and transportability. Internal–external validation involved dataset partitioning by time period and geographical region. Decision curve analysis was used to assess clinical utility.FindingsWe identified data for 11 626 969 female individuals, with 70 095 574 person-years of follow-up. There were 142 712 (1·2%) diagnoses of breast cancer, 24 043 (0·2%) breast cancer-related deaths, and 696 106 (6·0%) deaths from other causes. Meta-analysis pooled estimates of Harrell's C were highest for the competing risks model (0·932, 95% CI 0·917–0·946). The competing risks model was well calibrated overall (slope 1·011, 95% CI 0·978–1·044), and across different ethnic groups. Decision curve analysis suggested favourable clinical utility across all age groups. The XGBoost and neural network models had variable performance across age and ethnic groups.InterpretationA model that predicts the combined risk of developing and then dying from breast cancer at the population level could inform stratified screening or chemoprevention strategies. Further evaluation of the competing risks model should comprise effect and health economic assessment of model-informed strategies.FundingCancer Research UK.